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ASCO GU 2019

ASCO GU 2019: Early Tumor Shrinkage in the Phase III METEOR Study of Cabozantinib versus Everolimus in Advanced Renal Cell Carcinoma - An Analysis of Overall Survival

San Francisco, CA (UroToday.com) METEOR was a phase III study published in 2015 which compared cabozantinib to everolimus for patients with advanced or metastatic renal cell carcinoma (mRCC) who had progressed on at least one VEGFR-targeting tyrosine kinase inhibitor1. A total of 658 patients with randomized to receive cabozantinib 60 mg daily or everolimus 10 mg daily. In the final overall survival analysis, cabozantinib increased overall survival, delayed disease progression, and improved objective response compared with everolimus2. For patients receiving cabozantinib, median overall survival was 21.4 months, compared with 16.5 months in the everolimus arm. In 2016, the FDA approved cabozantinib for the treatment of patients with advanced RCC who had progressed on one prior line of anti-angiogenic therapy and based on the results of CABOSUN, the FDA approved cabozantinib for first line use in patients with intermediate or poor risk RCC.  In this abstract, analysis of the overall survival data is performed based on early tumor shrinkage. 

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During the study, imaging with CT/MRI was performed every 8 weeks for the first year, followed by every 12 weeks. Early tumor shrinkage (eTS) was defined as a decrease from in the sum of the longest diameter of target lesions at the first scan after starting therapy. Treatment was continued until unacceptable toxicity or progression and then the median overall survival was analyzed for all patients with an eTS ≥30%, any eTS at all, or no eTS.
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73.3% of patients had tumor shrinkage on cabozantinib, with 20% of patients having an eTS of 30% or greater, compared with 47.3% of patients having eTS on everolimus and only 5% with an eTS of 30% or more.  For patients with any eTS, median overall survival for patients on cabozantinib was 23.7 months, compared with 17.3 months for patients on everolimus (HR 0.62, p<0.05). For patients with ≥30% eTS, median OS was not reached for cabozantinib and 10.2 months for everolimus (HR 0.45, p<0.05). For patients without any eTS, there was no significant difference between patients receiving cabozantinib or everolimus.
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The majority of patients receiving cabozantinib will experience early tumor shrinkage and this is correlated with improved survival compared with patients with early tumor shrinkage on everolimus. However, there does not appear to be an OS benefit over everolimus if no eTS is seen. As expected, eTS is an indicator of clinical benefit. However, for patients without eTS, it is unknown what the optimal strategy should be as stable disease provides clinical benefit for many patients. 
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Presented by: Ignacio Duran, MD, PhD, Princess Margaret Cancer Centre, University of Toronto
Discussant:   Christian K. Kollmannsberger, MD—Chair

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, Twitter: @TheRealJasonZhu at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA

References:
  1. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma. The New England journal of medicine 2015;373:1814-23.
  2. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. The Lancet Oncology 2016;17:917-27.